This Shared Instrumentation Grant application is for the purchase of a Leica TCS SP2 laser scanning confocal microscope system. The instrument will be integrated into the Englert Cell Analysis Laboratory, which is a Shared Core Resource of the Norris Cotton Cancer Center at Dartmouth Medical School. The Englert Laboratory was establish3d in 1981 for flow cytometry and has been providing Dartmouth with imaging as well as flow cytometric instrumentation since 1993. The new confocal instrument will replace an outdated confocal system, giving users access to the stable, flexible, and up-to-date imaging capabilities that they require. The requirement for a new confocal system is based on several urgent needs. The existing confocal system does not have the laser stability or excitation and emission flexibility required for multicolor quantitative work by a varied and large group of users. In addition, there is an expressed need for live cell studies that cannot be met by the existing upright microscope stand lacking temperature control. Finally, a new system will have the ability to acquire images with 12 bit intensity resolution, will provide regions of interest for FRAP and inverse FRAP analysis, and will provide 4 PMTs for four color fluorescence acquisition-all of which are lacking on our current system and are required now by many users. A Leica TCS SP2 system will satisfy current users of the Core Facility and will provide flexibility for adaptation to the needs of users in the future. The Englert Cell Analysis Laboratory operates under the control of a Director, a Co-Director, and an Advisory Board, and with the technical support of a flow and an imaging supervisor. It is supported financially from the NCI core grant to the Norris Cotton Cancer Center, by hourly charges to users, and by institutional support from Dartmouth Medical School. At the present time, there are 33 NIH grant holders dependent upon the confocal system in the Englert Core Laboratory; they hold, as PIs, 50 NIH grants, with $9,918,884 in annual direct costs. A "major user group" has been identified. These eleven major users project 84% of the total use of the confocal system. They hold, as PIs, 20 NIH grants with $5,161, 571 in annual direct costs.